The long-term goal of the proposed research is the design and construction of a DNA sequencing system that can sequence the whole human genome under $100 including sample preparation and with the cost of goods of the system well under $10,000. The system developed under the proposed research is at least an order of magnitude in cost better than the target of the solicitation while maintaining all performance metrics. In that respect it will break the barrier towards genomic medicine. The overall system is based on optically sequencing DNA on a consumer cell-phone camera chip by means of a transducer that relates the nanometer scale dynamics of single base of a DNA to a macro-motion that is easy to image without the use of fluorescence, but only with a single common white-light LED. Preliminary data shows that the proposed method can already achieve DNA readlength of 1,600 bases and accurate sequencing alignment of 100 base sections. While this is a great start, Phase I work will continue to investigate the accuracy and readlength and throughput limits of this approach. To achieve that, software tools such as image processing and bioinformatics need to be constructed at this first phase, while at same time we will need to improve the biology assays. If successful, the main goal is to completely sequence a microbial DNA (Ecoli) at the end of Phase I, and thus completely benchmark the proposed architecture. Beyond Phase I, a low cost benchtop system will be constructed using commercial cell-phone camera chips and will be used to perform sequencing of Whole Human Genome with the target cost defined as goal of this grant solicitation.